Localization of deletion to a 300 Kb interval of chromosome 11q13 in cervical cancer

Abstract

Previous molecular genetic studies on HeLa cell (a cervical cancer cell line) derived non-tumorigenic and tumorigenic hybrids have localized a tumor suppressor gene to the long arm of chromosome 11. Analysis of cervical cancer cell lines using chromosome 11 specific probes showed deletion and translocation of 11q13 sequences in five out of eight cell lines. Fluorescence in situ hybridization (FISH), using 11q13 specific probes, has shown interstitial deletion of 11q13 sequences in the HeLa cells. In order to determine whether 11q13 deletions occur in primary cervical tumors, we analysed 36 tumors using 20 different microsatellite and RFLP markers. Semi automated fluorescein based allelotyping was performed to identify loss of heterozygosity (LOH) in tumors. The results showed allelic loss in 17 (47%) tumors. Three different regions of loss, one near MEN1, the second near D11S913, and the third near INT2 locus were observed. The smallest region of deletion overlap at the D11S913 locus was localized to a 300 Kb distance between D11S4908 and D11S5023. Fluorescence in situ hybridization (FISH), using 11q13 specific cosmid and BAC (bacterial artificial chromosome) probes, confirmed allelic deletion in the tumors. PCR analysis further identified homozygous deletion of 11q13 sequences in a primary tumor, in HeLa cells and in two HeLa cell derived tumorigenic hybrid cell lines. The homozygous deletion in the cell lines was mapped to a 5.7 kb sequence of 11q13. We hypothesize therefore that a putative cervical cancer tumor suppressor gene exists within the 300 kb of chromosome 11q13.

Methylation-dependent silencing of CST6 in primary human breast tumors and metastatic lesions

“…Furthermore, evidence from breast cancer cell lines suggests that CST6 promoter hypermethylation leading to gene silencing may represent one major mechanism for loss of cystatin M in breast cancer. CST6 is located in the chromosomal region 11q13, which is subject to amplification or loss of heterozygosity in several cancers (Cromer et al, 2004;Keppler, 2006;Srivatsan et al, 2002). Previously, we reported that the majority of CST6-negative breast cancer cell lines were originally established from metastatic lesions (pleural effusions) rather than primary breast tumors and that CST6-positive breast cancer cell line (BT-20) was derived from a primary breast carcinoma (Rivenbark et al, 2006a).…”

Deletion in chromosome 11 and Bcl-1/Cyclin D1 alterations are independently associated with the development of uterine cervical carcinoma

“…Nevertheless, the most essential factor implicated in the development of CA-CX is infection with HPV (Zur Hausen 1996). However, the discrepancy between high rates of HPV infection and low rates of cervical cancer development suggests that additional genetic alterations must also have a role in its development (Srivatsan et al 2002). Delineation of these genetic changes is crucial in understanding the molecular basis of cancer.…”

Frequent epigenetic inactivation of cystatin M in breast carcinoma

“…Cystatin M has been assigned to chromosome region 11q13, which is the site of loss of heterozygosity (LOH) in several cancer types and is believed to harbour tumour suppressor genes (Stenman et al, 1997;Srivatsan et al, 2002). Cystatin M regulates the activity of cathepsin B and cathepsin L, which are the two most important cysteine proteases implicated in tumour cell invasion and metastasis (Lah and Kos, 1998;Frosch et al, 1999).…”